Association between APOE e4 and white matter hyperintensity volume, but not total brain volume or white matter integrity

• Published in: Brain imaging and behavior Vol. 14; no. 5; pp. 1468 - 1476
• Main Authors: Lyall, Donald M., Cox, Simon R., Lyall, Laura M., Celis-Morales, Carlos, Cullen, Breda, Mackay, Daniel F., Ward, Joey, Strawbridge, Rona J., McIntosh, Andrew M., Sattar, Naveed, Smith, Daniel J., Cavanagh, Jonathan, Deary, Ian J., Pell, Jill P.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.10.2020; Springer Nature B.V
• Subjects: Age; Aging; Anisotropy; Apolipoprotein E4; Apolipoprotein E4 - genetics; Biomedical and Life Sciences; Biomedicine; Brain; Brain - diagnostic imaging; Cognitive ability; Confidence intervals; Cross-Sectional Studies; Dementia disorders; Deprivation; Diffusion Tensor Imaging; Genotype & phenotype; Genotypes; Hippocampus; Humans; Integrity; Magnetic Resonance Imaging; Medical imaging; Medicin och hälsovetenskap; Neuroimaging; Neuropsychology; Neuroradiology; Neurosciences; NMR; Nuclear magnetic resonance; Original Research; Phenotypes; Psychiatry; Risk acceptance; Risk analysis; Risk factors; Smoking; Statistical analysis; Statistical significance; Substantia alba; Substantia grisea; Substrates; United Kingdom; White Matter - diagnostic imaging; United Kingdom; United Kingdom > UK; Aging; Genetic association studies; APOE; MRI; Epidemiology
• ISSN: 1931-7557; 1931-7565; 1931-7565
• DOI: 10.1007/s11682-019-00069-9

Apolipoprotein ( APOE ) e4 genotype is an accepted risk factor for accelerated cognitive aging and dementia, though its neurostructural substrates are unclear. The deleterious effects of this genotype on brain structure may increase in magnitude into older age. This study aimed to investigate in UK Biobank the association between APOE e4 allele presence vs. absence and brain imaging variables that have been associated with worse cognitive abilities; and whether this association varies by cross-sectional age. We used brain magnetic resonance imaging (MRI) and genetic data from a general-population cohort: the UK Biobank ( N  = 8395 after exclusions). We adjusted for the covariates of age in years, sex, Townsend social deprivation scores, smoking history and cardiometabolic diseases. There was a statistically significant association between APOE e4 genotype and increased (i.e. worse) white matter (WM) hyperintensity volumes (standardised beta = 0.088, 95% confidence intervals = 0.036 to 0.139, P  = 0.001), a marker of poorer cerebrovascular health. There were no associations with left or right hippocampal, total grey matter (GM) or WM volumes, or WM tract integrity indexed by fractional anisotropy (FA) and mean diffusivity (MD). There were no statistically significant interactions with age. Future research in UK Biobank utilising intermediate phenotypes and longitudinal imaging hold significant promise for this area, particularly pertaining to APOE e4’s potential link with cerebrovascular contributions to cognitive aging.